In recent years, clinical studies regarding cell transplantation using stem cells have been vigorously carried out. Treatments such as peripheral vessel regeneration have been progressed using marrow monocytes or vascular endothelial progenitor cells. However, it has become clear that, after transplantation of cells, the transplanted cells engrafted into tissues at an extremely low survival rate, and this is considered problematic. Thus, an attempt to increase the survival rate or engrafted rate of the transplanted cells has been made by mixing a base material to which cells adhere, such as an extracellular matrix, with the cells to be transplanted, and then transplanting the thus obtained mixture. For instance, studies have been conducted to transplant mesenchymal cells together with a base material so as to treat cartilage. However, a majority of the studies have been at an animal experiment level. To date, there have been no reports providing revolutionary results.
Meanwhile, an amino acid, cysteine, has been known as a representative protecting group for protein oxidation. Cysteine has a free highly reactive SH group, and this SH group functions as a scavenger or reservoir for radicals and the like. In addition to such cysteine, methionine is also considered as an essential amino acid fur oxidative stress. There has been a report regarding methionine oxidation in proteins, demonstrating that methionine functions as an antioxidant amino acid (Non Patent Document 1).
Peptides or proteins comprising the oxidized methionine are described, for example, in Patent Documents 1 to 3. Patent Document 1 describes a synthetic cyclic peptide having a specific consensus sequence, in which a methionine residue is substituted with an oxidized methionine residue. Patent Document 2 describes a pharmaceutical product comprising thymosin β4, in which the methionine residue that is the 6th amino acid from the N-terminus is oxidized to methionine sulfoxide. Patent Document 3 describes a composition comprising a CTLA4-Ig molecule, in which approximately 2.5% or less of the cytotoxic T-lymphocyte antigen 4 (CTLA4)-Ig molecule is oxidized. However, none of the above-mentioned peptides or proteins has cellular adhesiveness.
Gelatin has been well known as a representative scaffolding material used in the field of regenerative medicine as a whole. Gelatin has been known as a highly biocompatible and highly safe material, and thus, it has been frequently applied for medical use. Also, collagen has been known as a proven material. However, collagen has solubility lower than that of gelatin, and it is highly restricted by the concentration and pH of a solution thereof (that is to say, collagen cannot be used to prepare a neutral solution of collagen having a high concentration of several tens of percent, etc.). Hence, products processable, producible, or moldable from collagen are generally limited. Accordingly, it has been desired to develop a scaffolding base material with improved cellular adhesiveness, which comprises gelatin.